Mortalin deficiency suppresses fibrosis and induces apoptosis in keloid spheroids.

Abstract

Mortalin (Mot) is a mitochondrial chaperone of the heat shock protein 70 family and it's pro-proliferative and anti-apoptosis functions could be associated with keloid pathogenesis, and blocking of mortalin and its interaction with p53 might be a potential novel target for the treatment of keloid. Therefore, we generated mortalin-specific small hairpin (sh) RNAs (dE1-RGD/GFP/shMot) and introduced into keloid spheroids for examination of its apoptotic and anti-fibrotic effect. On keloid tissues, mortalin expression was higher than adjacent normal tissues and it's protein expressions were activated keloid fibroblasts (KFs). After primary keloid spheroid were transduced with dE1-RGD/GFP/shMot for knockdown of mortalin, expression of type I, III collagen, fibronectin, and elastin was significantly reduced and transforming growth factor-β1, epidermal growth factor receptor (EGFR), Extracellular Signal-Regulated Kinases 1 and 2 (Erk 1/2), and Smad 2/3 complex protein expression were decreased. In addition, increased TUNEL activities and cytochrome C were observed. Further, for examine of mortalin and p53 interaction, we performed immunofluorescence analysis. Knockdown of mortalin relocated p53 to the cell nucleus in primary keloid spheroids by dE1-RGD/GFP/shMot transduction. These results support the utility of knockdown of mortalin to induce apoptosis and reduce ECMs expression in keloid spheroid, which may be highly beneficial in treating keloids.

• Authors: Won Jai Lee, Hyo Min Ahn, Youjin Na, Renu Wadhwa, JinWoo Hong, Chae-Ok Yun
• Journal: Scientific reports (Sci Rep) Vol. 7 Issue 1 Pg. 12957 (10 11 2017) ISSN: 2045-2322 [Electronic] England
• PMID: 29021584 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Collagen Type I
• Collagen Type III
• Fibronectins
• HSP70 Heat-Shock Proteins
• Proliferating Cell Nuclear Antigen
• RNA, Small Interfering
• Transforming Growth Factor beta
• Tumor Suppressor Protein p53
• mortalin
• Elastin
• ErbB Receptors
• Extracellular Signal-Regulated MAP Kinases

Topics

• Adenoviridae (metabolism)
• Apoptosis
• Cell Nucleus (metabolism)
• Collagen Type I (metabolism)
• Collagen Type III (metabolism)
• Elastin (metabolism)
• ErbB Receptors (metabolism)
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Fibroblasts (metabolism, pathology)
• Fibronectins (metabolism)
• Fibrosis
• HSP70 Heat-Shock Proteins (deficiency, metabolism)
• Humans
• Keloid (pathology)
• Proliferating Cell Nuclear Antigen (metabolism)
• Protein Binding
• RNA, Small Interfering (metabolism)
• Spheroids, Cellular (pathology)
• Transforming Growth Factor beta (metabolism)
• Tumor Suppressor Protein p53 (metabolism)